The present invention relates generally to apparatus and methods for formulation and solubility testing and ranking, and more specifically to apparatus and methods of using electro-osmotically driven systems for formulation mixing and measurement to produce rank orders of solubility for a variety of formulations and test media.
High throughput synthesis and screening are producing large numbers of potent and selective compounds, but more and more highly lipophilic compounds are emerging from these lead discovery initiatives. Many new lead compounds are relatively insoluble in water, which presents challenges in developing formulations for both oral and intravenous (TV) administration.
Choosing the right formulation can enhance the solubility of these poorly soluble drugs, improve the stability of unstable drugs, assist in controlling and sustaining the delivery of a particular drug, aid in targeted deliver, and minimize the pain during injection or minimize unwanted side effects. In a traditional drug development setting, formulation or test media development is a labor and time intensive task usually performed with several milligrams of compound.
Once compounds have been selected for development, formulating typically consists of dissolving compounds in water-miscible cosolvents--e.g., propylene glycol, polyethylene glycol, glycerin, ethanol, etc. Other methods of formulating water-insoluble drugs involve the use of solubilizing agents, detergents or altering the pH of the solutions. New formulation approaches include the use of emulsions, liposomes, nanospheres, and cyclodextrins (CDs).
The typical procedure for determining suitable formulations involves "dissolving" the compound into various formulations and using conventional analytical methodology for determining maximum concentrations. Analytical methods such as spectroscopic methods (UV-Vis) and high performance liquid chromatography (HPLC) are often used as well as visual examinations. Visual or spectroscopic methods require larger amounts of material.
The large number of lead compounds arising from combinatorial efforts in addition to the small quantities being synthesized have created a need for higher throughput formulating using small amounts of material. Formulating for in vivo testing using micrograms of material is quickly becoming a bottleneck for rapid assessment of a combinatorial chemistry drug's phannacokinetic profile and efficacy. Further, many of the compounds arising from combinatorial libraries are uncharged and highly lipophilic in nature and prevent the use of capillary zonal electrophoresis (CZE).
Hence, the invention is related to apparatus and methods which permit small amounts of material to be rapidly analyzed for solubility in a variety of test media, many of which are potential formulations.